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MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures

BACKGROUND: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer’s disease. Particularly, microRNA has been found li...

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Autores principales: Liu, Liqun, Liu, Lingjuan, Shi, Jiayun, Tan, Menglin, Xiong, Jie, Li, Xingfang, Hu, Qingpeng, Yi, Zhuwen, Mao, Ding’an
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981991/
https://www.ncbi.nlm.nih.gov/pubmed/27514646
http://dx.doi.org/10.1186/s12868-016-0291-6
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author Liu, Liqun
Liu, Lingjuan
Shi, Jiayun
Tan, Menglin
Xiong, Jie
Li, Xingfang
Hu, Qingpeng
Yi, Zhuwen
Mao, Ding’an
author_facet Liu, Liqun
Liu, Lingjuan
Shi, Jiayun
Tan, Menglin
Xiong, Jie
Li, Xingfang
Hu, Qingpeng
Yi, Zhuwen
Mao, Ding’an
author_sort Liu, Liqun
collection PubMed
description BACKGROUND: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer’s disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model. RESULTS: We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3. CONCLUSION: Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-016-0291-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-49819912016-08-13 MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures Liu, Liqun Liu, Lingjuan Shi, Jiayun Tan, Menglin Xiong, Jie Li, Xingfang Hu, Qingpeng Yi, Zhuwen Mao, Ding’an BMC Neurosci Research Article BACKGROUND: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer’s disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model. RESULTS: We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3. CONCLUSION: Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-016-0291-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-11 /pmc/articles/PMC4981991/ /pubmed/27514646 http://dx.doi.org/10.1186/s12868-016-0291-6 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Liu, Liqun
Liu, Lingjuan
Shi, Jiayun
Tan, Menglin
Xiong, Jie
Li, Xingfang
Hu, Qingpeng
Yi, Zhuwen
Mao, Ding’an
MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
title MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
title_full MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
title_fullStr MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
title_full_unstemmed MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
title_short MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
title_sort microrna-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981991/
https://www.ncbi.nlm.nih.gov/pubmed/27514646
http://dx.doi.org/10.1186/s12868-016-0291-6
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